Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptome-wide m6A profiles analysis in response to hypoxia

ABSTRACT: Recently, many studies have focused on the epigenetics such as histone modification and DNA methylation upon hypoxic stress. However, little is known about the the m6A epitranscriptome in response to hypoxia. In this study, we report that hypoxia systematically inhibit the m6A pathway through reducing the total m6A level and the expression of m6A readers. Deep m6A transcriptome sequencing revealed a drastic reprogramming of m6A epitranscriptome during cellular hypoxia. Integration m6A epitranscriptome with RNA-Seq or LC-MS/MS based proteome analysis of cells upon hypoxic stress revealed that the reprogramming of m6A epitranscriptome remodels the transcriptome and proteome to support the efficient generation of energy for adaption to hypoxia. Taken together, our studies indicated that the crosstalk between m6A and HIF1 pathway was essential for the cellular response to hypoxia, and provided profound insights into the molecular mechanism underlying the hypoxic responsive process.

ORGANISM(S): Homo sapiens

PROVIDER: GSE141941 | GEO | 2020/08/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Hypoxic stabilization of RIPOR3 mRNA via METTL3-mediated m6A RNA methylation drives breast tumor growth and metastasis [m6A-seq-sgControl and sgMETTL3]

Project description:N6-methyladenosine (m6A) modification is the most abundant internal mRNA modification in eukaryotes. Hypoxia induces reprogramming of m6A epitranscriptome, but the detail underlying regulator mechanism remains elusive in breast cancer. Here we reported that hypoxia induced elevated m6A modification involved in tumor progression. m6A- sequencing (m6A-seq) combined with RNA sequencing (RNA-seq) identified RIPOR3 as a key target gene of m6A modification under hypoxic stress. Hypoxia-induced increased of RIPOR3 m6A levels promoted its mRNA stability and expression, thereby facilitating the progression and metastasis of breast cancer. Besides, RIPOR3 was overexpressed in breast cancer cells and breast tumor tissues, and elevation of RIPOR3 expression was associated with poor prognosis. Mechanistically, RIPOR3 bound to EGFR and the interaction was enhanced under hypoxia, promoting the activation of the EGFR downstream PI3K-AKT signaling pathway. Altogether, our studies reveal that RIPOR3 responds to hypoxic stress to promote EGFR-PI3K-AKT signal pathway, facilitating breast cancer progression and metastasis, thus presenting itself as a potential therapeutic target.

2024-10-04 | GSE264247 | GEO

Hypoxic stabilization of RIPOR3 mRNA via METTL3-mediated m6A RNA methylation drives breast tumor growth and metastasis [m6A-seq-T47D]

2024-10-04 | GSE264245 | GEO

Viral and Cellular N6-methyladenosine (m6A) Epitranscriptomes in KSHV Life Cycle

Project description:Tan et al. discovered abundant conserved N6-methyladenosine (m6A) modifications on KSHV transcripts during latent and productive infection in different cell types. They also show that m6A readers YTHDF2 and YTHDF3 mediate KSHV replication, and KSHV optimizes both phases of viral replication by reprograming cellular epitranscriptome to regulate distinct signaling pathways.

2017-10-31 | GSE93676 | GEO

Physiologic Hypoxia Promotes Maintenance of CML Stem Cells Despite Effective BCR−ABL1 Inhibition

Project description:ABL1 kinase inhibitors such as imatinib mesylate (IM) are effective in managing chronic myelogenous leukemia (CML) but incapable of eliminating leukemia stem cells (LSCs), suggesting that kinase−independent pathways support LSC survival. Given that the bone marrow hypoxic microenvironment supports hematopoietic stem cells, we investigated if hypoxia similarly contributes to LSC persistence. Importantly, we found that while BCR−ABL1 kinase remained effectively inhibited by IM under hypoxia, apoptosis became partially suppressed. Furthermore, hypoxia enhanced the clonogenicity of CML cells, as well as their efficiency in repopulating immunodeficient mice, both in the presence and absence of IM. HIF1−α, which is the master regulator of the hypoxia transcriptional response is expressed in the bone marrow specimens of CML individuals. In vitro, HIF1−α is stabilized during hypoxia and its expression and transcriptional activity can be partially attenuated by concurrent IM treatment. Expression analysis demonstrates at the whole transcriptome level that hypoxia and IM regulate distinct subsets of genes. Functionally, knockdown of HIF1−α abolished the enhanced clonogenicity during hypoxia. Taken together, our results suggest that in the hypoxic microenvironment, HIF1−α signaling supports LSC persistence independently of BCR−ABL1 kinase activity. Thus targeting HIF1−α and its pathway components may be therapeutically important for the complete eradication of LSCs.

2014-06-03 | GSE48294 | GEO

LncRNA LUCAT1 Promotes Glioblastoma Progression by Enhancing HIF1⍺ Activity [ChIP-seq]

Project description:Glioblastoma (GBM) is characterized by a high degree of hypoxia. Hypoxia-inducible factors (HIFs) modulate glioma stem-like cell (GSC) responses to hypoxia and promote GBM progression, therapeutic resistance, and recurrence. Here we identify a new transcript of the long non-coding RNA LUCAT1 and show that it reinforces HIF1⍺ signaling in GSCs under hypoxia. LUCAT1 expression is highly induced under hypoxia in GBM and GSCs in a HIF1⍺-dependent manner. High LUCAT1 expression in human GBM correlates with increased aggression and poor survival. Mechanistically, LUCAT1 associates with chromatin and modulates interaction between HIF1⍺ and coactivator CBP to hypoxia response elements (HREs) to drive HIF1⍺-target gene expression under hypoxia. Thus, LUCAT1 acts as a positive feedback factor to augment HIF1⍺ signaling under hypoxic stress in GSCs. Loss of LUCAT1 reduces tumor growth and prolongs mouse survival in xenograft models of GBM. Our findings provide new insights into how GSCs regulate gene expression under hypoxia and identify LUCAT1 as therapeutic target in GBM.

2024-03-12 | GSE255502 | GEO

LncRNA LUCAT1 Promotes Glioblastoma Progression by Enhancing HIF1⍺ Activity [RNA-seq]

2024-03-12 | GSE255501 | GEO

The retinoblastoma protein regulates hypoxia-inducible genetic programs, tumor cell invasiveness and neuroendocrine differentiation in prostate cancer cells

Project description:Loss of tumor suppressor proteins, such as the retinoblastoma protein (Rb), results in tumor progression and metastasis. Metastasis is facilitated by low oxygen availability within the tumor that is detected by hypoxia inducible factors (HIFs). The HIF1 complex, HIF1Î± and dimerization partner the aryl hydrocarbon receptor nuclear translocator (ARNT), is the master regulator of the hypoxic response. Previously, we demonstrated that Rb represses the transcriptional response to hypoxia by virtue of its association with HIF1. In this report, we further characterized the role of Rb in HIF1-regulated genetic programs by stably ablating Rb expression with retrovirally-introduced short hairpin RNA in LNCaP and 22Rv1 human prostate cancer cells. DNA microarray analysis revealed that Rb regulates specific chromosomal gene clusters and loss of Rb in conjunction with hypoxia leads to dysregulation of HIF1-regulated genetic programs that increase cell invasion and promote neuroendocrine differentiation. For the first time, we have established a direct link between hypoxic tumor environments, Rb inactivation and progression to late stage metastatic neuroendocrine prostate cancer. Understanding the molecular pathways responsible for progression of benign prostate tumors to metastasized and lethal forms will aid in the development of more effective prostate cancer therapies. RNAs derived from human LNCaP cells stably infected with either scrambled control shRNA or a shRNA directed to RB1. Cells were exposed to either 24 h hypoxia (1% O2) or maintained under normoxic conditions. Biological triplicates were tested and compared.

2016-02-24 | E-GEOD-78245 | biostudies-arrayexpress

Refined RIP-seq protocol for epitranscriptome analysis with low input materials

Project description:We optimized the key parameters of m6A MeRIP-seq, including the starting amount of RNA, RNA fragmentation, antibody selection, MeRIP washing/elution conditions, methods for RNA library construction and the bioinformatics analysis pipeline. With the optimized immunoprecipitation conditions and a post-amplification rRNA depletion strategy, we were able to profile the m6A epitranscriptome using 2 µg of total RNA. We identified ~12,000 m6A peaks with a high signal/noise ratio from two lung adenocarcinoma (ADC) patient tumors. Through integrative analysis of the transcriptome, m6A epitranscriptome and proteome data in the same patient tumors, we identified dynamics at the m6A level that accounts for the discordance between mRNA and protein levels in these tumors.

2018-09-06 | GSE116002 | GEO

MITF controls the TCA cycle to modulate the melanoma hypoxia response

Project description:In response to the dynamic intra-tumor microenvironment, melanoma cells adopt different phenotypic states possessing distinct biological properties associated with differential expression of the microphthalmia-associated transcription factor (MITF). The response to hypoxia, a major microenvironmental cue, is underpinned by expression of hypoxia-inducible transcription factors (HIFs) that reprogram metabolism and promote pro-angiogenic VEGF expression. HIF1 indirectly represses MITF via the transcription factor bHLHE40/DEC1, and MITF can activate HIF1 expression. Although HIF and MITF share a highly related DNA-binding specificity, it is unclear whether they share a subset of target genes. Moreover, the genome-wide impact of hypoxia on melanoma, which genes are direct HIF targets, and whether melanoma cell lines representing different phenotypic states exhibit distinct hypoxic responses is unknown. Here we show, that three different melanoma cell lines exhibit widely different hypoxia responses with only a core 23 genes regulated in common after 12 h in hypoxia. Surprisingly, under hypoxia MITF is transiently up-regulated by HIF1 and co-regulates a subset of HIF targets including VEGFA. Significantly, we also show that MITF represses itself and also regulates SDHB to control the TCA cycle and suppress pseudo-hypoxia. Our results reveal a previously unsuspected role for MITF in metabolism and the network of factors underpinning the hypoxic response in melanoma.

2019-06-13 | GSE132624 | GEO

The retinoblastoma protein regulates hypoxia-inducible genetic programs, tumor cell invasiveness and neuroendocrine differentiation in prostate cancer cells

Project description:Loss of tumor suppressor proteins, such as the retinoblastoma protein (Rb), results in tumor progression and metastasis. Metastasis is facilitated by low oxygen availability within the tumor that is detected by hypoxia inducible factors (HIFs). The HIF1 complex, HIF1α and dimerization partner the aryl hydrocarbon receptor nuclear translocator (ARNT), is the master regulator of the hypoxic response. Previously, we demonstrated that Rb represses the transcriptional response to hypoxia by virtue of its association with HIF1. In this report, we further characterized the role of Rb in HIF1-regulated genetic programs by stably ablating Rb expression with retrovirally-introduced short hairpin RNA in LNCaP and 22Rv1 human prostate cancer cells. DNA microarray analysis revealed that Rb regulates specific chromosomal gene clusters and loss of Rb in conjunction with hypoxia leads to dysregulation of HIF1-regulated genetic programs that increase cell invasion and promote neuroendocrine differentiation. For the first time, we have established a direct link between hypoxic tumor environments, Rb inactivation and progression to late stage metastatic neuroendocrine prostate cancer. Understanding the molecular pathways responsible for progression of benign prostate tumors to metastasized and lethal forms will aid in the development of more effective prostate cancer therapies.

2016-02-24 | GSE78245 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data